Isolation of Nocuolin A and Synthesis of New Oxadiazine Derivatives. Design, Synthesis, Molecular Docking, Apoptotic Evaluation, and Cathepsin B Inhibition
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Published:2023-04-29
Issue:5
Volume:21
Page:284
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ISSN:1660-3397
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Container-title:Marine Drugs
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language:en
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Short-container-title:Marine Drugs
Author:
Tena Pérez Víctor1, Apaza Ticona Luis12ORCID, H. Cabanillas Alfredo1, Maderuelo Corral Santiago3, Rosero Valencia Diego Fernando3, Martel Quintana Antera4ORCID, Ortega Domenech Montserrat3, Rumbero Sánchez Ángel1
Affiliation:
1. Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, 28049 Madrid, Spain 2. Organic Chemistry Unit, Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy, University Complutense of Madrid, Plza. Ramón y Cajal s/n, 28040 Madrid, Spain 3. VALORALIA I MÁS D, SL, Tres Cantos, 28760 Madrid, Spain 4. Spanish Bank of Algas, Institute of Oceanography and Global Change (IOCAG) University of Las Palmas de Gran Canarias, Muelle de Taliarte s/n, 35214 Telde, Canary Islands, Spain
Abstract
Nocuolin A (1), an oxadiazine, was isolated from the cyanobacterium Nostoc sp. Its chemical structure was elucidated using NMR and mass spectroscopic data. From this compound, two new oxadiazines, 3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropyl acetate (2) and 4-{3-[(6R)-5,6-dihydro-4,6-dipentyl-2H-1,2,3-oxadiazin-2-yl]-3-oxopropoxy}-4-oxobutanoic acid (3), were synthesised. The chemical structures of these two compounds were elucidated by a combination of NMR and MS analysis. Compound 3 showed cytotoxicity against the ACHN (0.73 ± 0.10 μM) and Hepa-1c1c7 (0.91 ± 0.08 μM) tumour cell lines. Similarly, compound 3 significantly decreased cathepsin B activity in ACHN and Hepa-1c1c7 tumour cell lines at concentrations of 1.52 ± 0.13 nM and 1.76 ± 0.24 nM, respectively. In addition, compound 3 showed no in vivo toxicity in a murine model treated with a dose of 4 mg/kg body weight.
Funder
VALORALIA I MÁS D, SL
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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